Genetic Testing Can Reduce Suffering and Save Lives
I am Oneinforty. In late 2016 at the age of 45, I sought genetic counseling and screening after a friend’s urging. The screening showed I had inherited a BRCA gene mutation, putting my lifetime risk of developing breast cancer between 50% and 80%1 and my lifetime risk of developing ovarian cancer (for which there is limited screening) between 40% and 60%.2
I was advised to have my fallopian tubes and ovaries removed—relatively easy same-day surgery that would have dramatically reduced my risk of developing ovarian cancer. But it was too late. Around the same time, I had magnetic resonance imaging (MRI) to determine the cause of severe back pain I had been experiencing for weeks. The MRI revealed an incidental finding of what turned out to be stage IV ovarian cancer. Given my family history of breast cancer on my father’s side, coupled with my Ashkenazi (ie, Eastern European) Jewish heritage, my father and I should have been referred to genetic counselors and offered screening for BRCA gene mutations many years ago. While undergoing my first course of treatment, I discovered that most people with Ashkenazi Jewish heritage are unaware that their risk of inheriting a BRCA gene mutation is 1:40, which is 10 times higher than that of the general population.3
BRCA gene mutations put people at heightened risk of cancers including male/female breast cancer, ovarian cancer, and prostate cancer. If you know you are BRCA positive, you can often reduce your risk of developing a BRCA cancer or detect it early through enhanced screening, risk-reducing surgery, and/or chemoprevention. I founded Oneinforty (www.oneinforty.org), a Massachusetts-based nonprofit organization,4 with a mission to prevent what happened to me and my family from happening to anyone else.
Oneinforty has learned that, surprisingly, most primary care physicians (PCPs) are not aware of the 1:40 risk of a BRCA mutation faced by their patients who have at least 1 Ashkenazi Jewish grandparent. Because of this lack of awareness, physicians do not routinely offer our high-risk population genetic counseling and screening. Consequently, most BRCA-positive men and women learn that they have a BRCA gene mutation only after receiving an advanced-stage cancer diagnosis and/or losing loved ones to the BRCA cancers. Compounding the problem is the fact that many PCPs are not familiar with nuances of BRCA such as:
• Half of people with a BRCA gene mutation have no known family history of the associated cancers.
• Men are as likely as women to both inherit and pass on BRCA gene mutations to their sons and daughters.
• Just 1 parent need be BRCA positive for each of a couple’s sons and daughters to have a 50% chance of being BRCA positive.
Oneinforty is working tirelessly to educate PCPs and influence national healthcare policy and practice reform to increase the prevention and detection of BRCA cancer.
A genetic counselor who serves on Oneinforty’s medical advisory board recently prepared a literature review for us containing some of the myriad seminal studies that support population-based screening for patients with Ashkenazi Jewish heritage. These include as follows:
1. Gabai-Kapar et al; 2014. The authors concluded that population-based screening would identify many carriers who are not evaluated by genetic testing based on family history criteria.5
2. Manchanda et al; 2015. Using a decision analytic model, the investigators showed that population-based screening would save more lives than family history-based screening; the lifetime cost savings would be £3.7 million ($4.61 million). Population-based screening would likely result in even higher lifetime savings today, because the cost of BRCA gene mutation testing has fallen considerably in the past several years.6
3. Manchanda et al; 2017. Findings support population-based testing for women who have 1 to 4 Ashkenazi Jewish grandparents.7
4. Lieberman et al; 2017. This qualitative study assessed a streamlined process that offered written pre-test information only, followed by genetic testing, with access to post-test genetic counseling. This process was viewed favorably by most individuals, suggesting a novel way to reduce barriers and expand access.8
5. Lieberman et al; 2018. Results showed that universal screening circumvents dependence on family disclosure, which at best is typically no higher than 50% for close relatives and significantly lower for more extended relatives who may still be at increased risk.9
Landmark studies such as those have shown that—compared with family history–based screening—population-based screening results in no lasting, undue psychiatric harm and:
• Makes economic sense
• Gives families agency over their own health
• Reduces BRCA cancer diagnoses
• Saves more lives
Since Oneinforty’s launch 2 years ago, the organization has accomplished far more than I could have imagined.
• Through our efforts, we have reached more than 700 people with lifesaving information presented by panelists representing medical institutions, genetic counselors, mental health professionals, and “I am Oneinforty” storytellers.
• Feedback from our symposia has been universally positive, including comments such as “Very moving and thought-provoking” and “great mix of medical, clinical, and personal speakers.” Data show attendees’ increased knowledge and intention to take action based on information presented.
• Through our new Medical Education Program, we have educated nearly 100 physicians at Massachusetts General Hospital and Newton-Wellesley Hospital about the 1:40 BRCA-positive risk faced by families with Ashkenazi Jewish heritage.
• Establishment of the Prevent Hereditary Cancer Coalition has brought together a diverse group of organizations and individual leaders from around the world committed to healthcare policy and practice reform related to the prevention of hereditary cancer.
• Backed by evidence-based research, we presented at the National Comprehensive Cancer Network (NCCN) Patient Advocacy Summit last December, requesting an expansion of national clinical practice guidelines to include routine screening for the BRCA founder gene mutations of men and women with at least 1 Ashkenazi Jewish grandparent, regardless of known family history. Our request was formally presented to NCCN’s Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer panel earlier this year and is under review.
• Media outreach about Oneinforty’s important mission and messages has reached tens of thousands through coverage by media outlets such as the The Boston Globe, The New York Times, The Times of Israel, The Jewish Advocate, Shalom Magazine, and WCVB-TV (Boston, Massachusetts).
• The Oneinforty.org website and BRCAlert e-newsletter provide resources and information of benefit to families at risk of hereditary cancer syndrome.
In December 2017, I had a recurrence of the ovarian cancer and received a second course of chemotherapy. This past January, while driving with our 4-year-old son, I had a seizure caused by a brain tumor that turned out to be metastasized ovarian cancer. Fortunately, before losing consciousness, I pulled off the highway and asked a Good Samaritan to call 911. I had a successful craniotomy followed by radiation to my brain. I currently have a handful of malignant lymph nodes in my abdomen and pelvis and am on a poly ADP ribose polymerase (PARP) inhibitor, a breakthrough targeted therapy designed to treat and delay recurrence. Epilepsy and a blood-clotting disorder, both recent unexpected diagnoses stemming from the ovarian cancer, have made my medical situation and life far more complex and challenging.
Building Oneinforty has been the best “medicine” for me and my loved ones. We regularly hear from men and women who have learned of their hereditary cancer risk from Oneinforty and decided to get screened for the BRCA gene mutations. Most are 39:40 and relieved to find out that they are BRCA negative. Of course, some of these individuals such as these discovered that hereditary cancer syndrome runs in their family:
My mom has a BRCA gene mutation and is an ovarian cancer survivor. With guidance and support from Oneinforty, I found out that I too am BRCA positive. I’m glad to have this information and to begin my journey of informed medical decision making to reduce my risk of developing breast and ovarian cancer. I’m also grateful to be able to help my school-age son and daughter face their BRCA risk when they grow up.
If it weren’t for Oneinforty, I wouldn’t have sought genetic counseling and testing and discovered that I have a genetic mutation that puts me at increased risk for colorectal cancer. My first colonoscopy revealed a very large polyp that contained precancerous cells. Now I have regular colonoscopies and am in a position to educate my sons, siblings, and parents about their hereditary cancer risk.
Would you touch base with my wife? She may be BRCA positive. We just heard yesterday. Really might not have been tested if not for your talk! Obviously, we are still processing. We have not told anyone, including our 2 daughters who are 20 and 22.
These Oneinforty constituents are grateful for the opportunity to make action plans with their physicians to manage their cancer risk and inform family members who may be affected. We remind BRCA-positive individuals who are overwhelmed by the diagnosis that they were BRCA positive since birth and that knowledge typically proves empowering.
George Washington University’s Milken Institute of Public Health says on its website:
Understanding the difference between health equality and health equity is important to public health to ensure that resources are directed appropriately—as well as supporting the ongoing process of meeting people where they are.…For these reasons, providing the same type and number of resources to all is not enough.
In order to reduce the health disparities gap, the underlying issues and individual needs of underserved and vulnerable populations must be effectively addressed.10
There is clearly a gross inequality here: Patients with Ashkenazi Jewish ancestry are at least 10 times more likely than members of the general population to be BRCA positive. Oneinforty is illuminating a related and glaring healthcare inequity—namely, it is not standard of care to identify members of this high-risk population; inform them of their risk; educate them about managing their risk; and offer them ready, affordable access to emotional support, genetic counseling, and BRCA screening.
Oneinforty advocates for all families in which a BRCA gene mutation is lurking. We are Oneinforty, and we need the US healthcare system to meet us where we are: largely uninformed, underserved, grief-stricken, and anxious to face our high risk of having hereditary cancer syndrome. We should routinely be given the opportunity to find out our BRCA status before cancer strikes. From personal experience, I know that—as scary as the risk of having a BRCA gene mutation may feel—hearing the words “You have cancer” is far more devastating and life altering.